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This clinical trial is performed with patients with knee osteoarthritis who were radiologically diagnosed with Kellgren-Lawrence (K&L) grade 2 or 3. Subjects who voluntarily signed consent form and met inclusion/exclusion criteria, were evaluated eligible and participated in this trial. Investigator selected knee to be evaluated (right or left) and administered investigational product to selected knee on Day 1.
A total of 3 or 6 subjects will be enrolled in low-dose or mid-dose group each, and 6 subjects will be enrolled in high-dose group. The study used a dose escalation scheme (from low-dose to high-dose) to determine the maximum tolerated dose (MTD).
All subjects in each dose-group will visit 1 month* (visit 5, 1 month±5 days) after administration of investigational product to evaluate dose limit toxicity (DLT) and determine whether to drop or proceed to next dose level.
Total 5 visit (1week, 1 month, 2 months, 3 months, 6 months) until 6 months after administration of investigational product is planned to assess safety through vial sign, laboratory tests, and exploratory efficacy of IP will be assessed through Western Ontario and McMaster Universities osteoarthritis index (WOMAC), 100-mm visual analogue scale (VAS) and International Knee Documentation Committee (IKDC) subjective knee evaluation.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| SMUP-IA-01(low-dose) | Experimental | A single knee administration of SMUP-IA-01 (low-dose, 4.0 x 10^6 cells/2mL) (2 ml of 1% sodium hyaluronate injection is administered before administration of SMUP-IA-01) |
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| SMUP-IA-01(mid-dose) | Experimental | A single knee administration of SMUP-IA-01 (mid-dose, 1.0 x 10^7 cells/2mL) ( 2 ml of 1% sodium hyaluronate injection is administered before administration of SMUP-IA-01) |
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| SMUP-IA-01(high-dose) | Experimental | A single knee administration of SMUP-IA-01 (high-dose, 2.0 x 10^7 cells/2mL) (2 ml of 1% sodium hyaluronate injection is administered before administration of SMUP-IA-01) |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| SMUP-IA-01(low-dose) | Biological | A single knee administration of SMUP-IA-01(low-dose, 4.0 x 10^6 cells/2mL) |
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| Measure | Description | Time Frame |
|---|---|---|
| Change of total score in WOMAC (Western Ontario and McMaster University Osteoarthritis Index) compared to baseline at 6 months after treatment | Change of total scorein WOMAC compared to baseline at 6 months after treatment. WOMAC consists of three subscales: pain, stiffness, and physical function, and is performed on baseline (visit 2) and final (Visit 8) visits. Total of 24 questions are evaluated with 5 questions for pain, 2 questions for stiffness, and 17 questions for physical function. Each question is scored between 0 point (no symptom) ~ 4 points (severe symptoms) scale, and the total score is between 0 point (no symptoms) ~ 96 points (higher score representing worse symptoms). | Baseline, Month 6 |
| Measure | Description | Time Frame |
|---|---|---|
| Change of score in WOMAC three subscales (Pain, stiffness, physical function)compared to baseline at 6 months after treatment | The WOMAC measures five items for pain (score range 0-20), two for stiffness (score range 0-8), and 17 for functional limitation (score range 0-68). | Baseline, Month 6 |
| Change of score in 100 mm VAS (Visual Analogue Scale) compared to baseline |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Myungchul Lee, MD, PhD | Seoul National University Hospital | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Seoul National University Hospital | Seoul | Jongno-gu | 03080 | South Korea |
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| ID | Term |
|---|---|
| D020370 | Osteoarthritis, Knee |
| ID | Term |
|---|---|
| D010003 | Osteoarthritis |
| D001168 | Arthritis |
| D007592 | Joint Diseases |
| D009140 | Musculoskeletal Diseases |
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| SMUP-IA-01(mid-dose) | Biological | A single knee administration of SMUP-IA-01(mid-dose, 1.0 x 10^7 cells/2mL) |
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| SMUP-IA-01(high-dose) | Biological | A single knee administration of SMUP-IA-01(high-dose, 2.0 x 10^7 cells/2mL) |
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The VAS is a horizontal line, 100 mm in length and anchored by word descriptors at each end (no pain, very severe pain). The patient marks on the line at the point that represents their current state. The VAS score is determined by measuring in millimeters from the left hand end to the point of the mark. The score ranges from "0" or no pain to "100" very severe pain. |
| Baseline, Month 1, Month 2, Month 3, Month 6 |
| Change of score in IKDC(International Knee Documentation Committee)compared to baseline | Change of score in IKDC compared to baseline. IKDC subjective knee evaluation consists of three categories: symptoms, sports activities, and functions. For each category, there are 7 questions for symptoms, 2 questions for sports activities, and 2 questions for functions, a total of 11 questions for evaluation. The scores for each category are summed up and divided into 87, which is the maximum score possible, and then is evaluated by converting it into a scale of 100 points. Higher score indicates better function and less symptoms for the knee. | Baseline, Month 1, Month 2, Month 3, Month 6 |
| Change of score in WORMS(Whole-Organ Magnetic Resonance iMaging Score) compared to baseline at 6 months after treatment | For structural and tissue evaluation of knee, MRI image of detailed knee parts are graded from min. 0 to max. 6. Lower number indicate normal status | Baseline, Month 6 |
| Change in K&L(Kellgren-Lawrence) grade compared to the baseline at 3 months and 6 months after treatment | The K & L grade is 0 to 4 Grade, which means that the higher the grade, the greater the joint damage and the stenosis of the joint. | Baseline, Month 3, Month 6 |
| Change in joint space width compared to the baseline at 3 months and 6 months after treatment | Evaluation of disease progression in target knee as ascertained by change from baseline in joint space width (JSW) determined using radiography | Baseline, Month 3, Month 6 |
| Change in mechanical axis, anatomical axis compared to the baseline at 3 months and 6 months after treatment | The degree of deformation of the lower half of the body is measured by measuring the angles of the mechanical axis and the anatomical axis with respect to the vertical axis. Mechanical axis: A line connecting the femoral head center point and the ankle joint center point. Anatomical axis: The middaphyseal line of the femur and tibia. | Baseline, Month 3, Month 6 |
| D012216 |
| Rheumatic Diseases |